| 1 | Plos Biol。2007年11月5日：E297 |
|---|---|
| PMID | 18001149 |
| Title | Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype. |
| 抽象的 | 预硫次抑制（PPI）的缺陷是生物学标记精神分裂症。解开控制PPI的机制,我们performed quantitative trait loci (QTL) analysis on 1,010 F2 mice derived by crossing C57BL/6 (B6) animals that show high PPI with C3H/He (C3) animals that show low PPI. We detected six major loci for PPI, six for the acoustic startle response, and four for latency to response peak, some of which were sex-dependent. A promising candidate on the Chromosome 10-QTL wasFABP7（脂肪酸结合蛋白7，脑），一种与N-甲基-D-天冬氨酸（NMDA）受体和星形胶质细胞中表达的功能联系的基因。FABP7-deficient mice showed decreased PPI and a shortened startle response latency, typical of the QTL's proposed effects. A quantitative complementation test supportedFABP7作为潜在的PPI-QTL基因，特别是在雄性小鼠中。破坏FABP7attenuated neurogenesis in vivo. HumanFABP7显示出改变的表达精神分裂症大脑和遗传关联与精神分裂症, which were both evident in males when samples were divided by sex. These results suggest thatFABP7plays a novel and crucial role, linking the NMDA, neurodevelopmental, and glial theories of精神分裂症病理和PPI内表型，在男性中具有更大或明显的影响。我们还从胎儿编程的角度讨论结果。 |
| SCZ Keywords | 精神分裂症，精神分裂症 |
| 2 | Plos Biol。2007年11月5日：E297 |
| PMID | 18001149 |
| Title | Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype. |
| 抽象的 | 预硫次抑制（PPI）的缺陷是生物学标记精神分裂症。解开控制PPI的机制,我们performed quantitative trait loci (QTL) analysis on 1,010 F2 mice derived by crossing C57BL/6 (B6) animals that show high PPI with C3H/He (C3) animals that show low PPI. We detected six major loci for PPI, six for the acoustic startle response, and four for latency to response peak, some of which were sex-dependent. A promising candidate on the Chromosome 10-QTL wasFABP7（脂肪酸结合蛋白7，脑），一种与N-甲基-D-天冬氨酸（NMDA）受体和星形胶质细胞中表达的功能联系的基因。FABP7-deficient mice showed decreased PPI and a shortened startle response latency, typical of the QTL's proposed effects. A quantitative complementation test supportedFABP7作为潜在的PPI-QTL基因，特别是在雄性小鼠中。破坏FABP7attenuated neurogenesis in vivo. HumanFABP7显示出改变的表达精神分裂症大脑和遗传关联与精神分裂症, which were both evident in males when samples were divided by sex. These results suggest thatFABP7plays a novel and crucial role, linking the NMDA, neurodevelopmental, and glial theories of精神分裂症病理和PPI内表型，在男性中具有更大或明显的影响。我们还从胎儿编程的角度讨论结果。 |
| SCZ Keywords | 精神分裂症，精神分裂症 |
| 3 | PLoS ONE 2009 -1 4: e5085 |
| PMID | 19352438 |
| Title | Arachidonic acid drives postnatal neurogenesis and elicits a beneficial effect on prepulse inhibition, a biological trait of psychiatric illnesses. |
| 抽象的 | Prepulse inhibition (PPI) is a compelling endophenotype (biological markers) for mental disorders including精神分裂症。In a previous study, we identifiedFABP7, a fatty acid binding protein 7 as one of the genes controlling PPI in mice and showed that this gene was associated with精神分裂症。我们还证明了破坏FABP7dampened hippocampal neurogenesis. In this study, we examined a link between neurogenesis and PPI using different animal models and exploring the possibility of postnatal manipulation of neurogenesis affecting PPI, since gene-deficient mice show biological disturbances from prenatal stages. In parallel, we tested the potential for dietary polyunsaturated fatty acids (PUFAs), arachidonic acid (ARA) and/or docosahexaenoic acid (DHA), to promote neurogenesis and improve PPI. PUFAs are ligands for Fabp members and are abundantly expressed in neural stem/progenitor cells in the hippocampus. Our results are: (1) an independent model animal, Pax6 (+/-) rats, exhibited PPI deficits along with impaired postnatal neurogenesis; (2) methylazoxymethanol acetate (an anti-proliferative drug) elicited decreased neurogenesis even in postnatal period, and PPI defects in young adult rats (10 weeks) when the drug was given at the juvenile stage (4-5 weeks); (3) administering ARA for 4 weeks after birth promoted neurogenesis in wild type rats; (4) raising Pax6 (+/-) pups on an ARA-containing diet enhanced neurogenesis and partially improved PPI in adult animals. These results suggest the potential benefit of ARA in ameliorating PPI deficits relevant to psychiatric disorders and suggest that the effect may be correlated with augmented postnatal neurogenesis. |
| SCZ Keywords | 精神分裂症，精神分裂症 |
| 4 | J. Hum. Genet. 2010 Feb 55: 127-30 |
| PMID | 20057506 |
| Title | Polymorphism screening of brain-expressed FABP7, 5 and 3 genes and association studies in autism and schizophrenia in Japanese subjects. |
| 抽象的 | 脂肪酸结合蛋白（FABP）基因家族编码脂肪酸结合蛋白，至少由12个成员组成FABP7, 5 and 3 are expressed in the brain. We previously showed thatFABP7与..相联系精神分裂症和躁郁症。最近，自闭症与精神分裂症has been reported. Therefore, in this study, we set out to examine the possible roles of brain-expressed FABPs in autism, focusing primarily on potentially functional polymorphisms (that is, missense polymorphisms). First, we resequenced the three genes using 285 autism samples. We identified 13 polymorphisms, of which 7 are novel. Of the novel single-nucleotide polymorphisms (SNPs), two are missense mutations, namely, 376G>C (Val126Leu) inFABP7and 340G>C (Gly114Arg) in FABP5. Second, we tested for the genetic association of four missense SNPs with autism and精神分裂症, but failed to detect significant results. Finally, as a web-based algorithm predicts that the 8A>G (Asp3Gly; rs17848124) in FABP3 is 'probably damaging', we estimated the possible impact of this SNP, and found that the loss of charge and salt bridge, caused by the Asp3-to-Gly3, may affect stability of the FABP3 protein. Future searches for associated phenotypes with missense SNPs using larger samples are highly warranted. |
| SCZ Keywords | 精神分裂症，精神分裂症 |
| 5 | Brain Nerve 2010 12月62日：1315-22 |
| PMID | 21139184 |
| Title | [产后神经发生的分子机制和心理功能]。 |
| 抽象的 | Postnatal neurogenesis has been observed in two brain regions: the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus, among vertebrates including human. Accumulating evidence has indicated the molecular mechanisms commonly underlying embryonic and adult neurogenesis. Genetic factors essential for neural development, i.e., Pax6,FABP7，Sox2，Wnt3，Notch1等也在成人神经源性区域中表达。然而，成年神经发生与胚胎神经发生不同，因为前者是活性依赖的。环境刺激调节成人神经发生的整个过程。在海马中，体育锻炼和认知刺激可稳健地增加前体细胞的增殖，而身体/社会心理应激会降低新生神经元的增殖。因此，成年神经发生受到几个遗传和环境因素的调节。在某些精神疾病的动物模型（例如精神分裂症and major depression, implicating that postnatal neurogenesis may contribute to a part of the symptoms of mental illness. In this review, we describe the molecular mechanisms and functional significance of postnatal neurogenesis. |
| SCZ Keywords | 精神分裂症，精神分裂症 |
| 6 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2010 Mar 153B: 484-93 |
| PMID | 19554614 |
| Title | 脑表达的脂肪酸结合蛋白（FABP）基因与精神分裂症和双相情感障碍之间的关联分析。 |
| 抽象的 | 抑制前抑制作用（PPI）是精神病的生物学标志物，例如精神分裂症和躁郁症。为了阐明PPI控制机制，我们先前在小鼠中进行了定量性状基因座（QTL）分析，并确定FABP7，将脑型脂肪酸结合蛋白（FABP）编码为致病基因。在这项研究中，人类FABP7showed genetic association with精神分裂症。FABPs constitute a gene family, of which members FABP5 and FABP3 are also expressed in the brain. These FABP proteins are molecular chaperons for polyunsaturated fatty acids (PUFAs) such as arachidonic and docosahexaenoic acids. Additionally, the involvement of PUFAs has been documented in the pathophysiology of精神分裂症and mood disorders. Therefore in this study, we examined the genetic roles of FABP5 and 3 in精神分裂症结合控制(N = 1900)dFABP7, 5, and 3 in bipolar disorder (N = 1,762 in the case-control set). Three single nucleotide polymorphisms (SNPs) fromFABP7showed nominal association with bipolar disorder, and haplotypes of the same gene showed empirical associations with bipolar disorder even after correction of multiple testing. We could not perform association studies on FABP5, due to the lack of informative SNPs. FABP3 displayed no association with either disease. Each FABP is relatively small and it is assumed that there are multiple regulatory elements that control gene expression. Therefore, future identification of unknown regulatory elements will be necessary to make a more detailed analysis of their genetic contribution to mental illnesses. |
| SCZ Keywords | 精神分裂症，精神分裂症 |
| 7 | Front Behav Neurosci 2014 -1 8：388 |
| PMID | 25414651 |
| Title | 成瘾和与奖励相关的基因在产后核核中显示出改变的表达。 |
| 抽象的 | 孕产涉及自然奖励的转变，从而使后代变得高度收获。伏隔核（NAC）是自然奖励和成瘾的关键中枢神经系统区域，但迄今为止，尚无大规模评估NAC中的事件，这是自然奖励的产妇变化的基础。在这项研究中，我们利用微阵列和生物信息学方法来评估小鼠产后NAC基因表达变化。模块化的单集富集测试（MSET）表明，在五个独立策划的数据库中的五个（例如，malacards，phenopedia）中的五个中的五个中，与成瘾和奖励有关的基因和奖励相关的基因和奖励相关的基因和奖励都显着富集了产后（相对于Virgin）NAC基因表达谱。Over 100 addiction/reward related genes were identified and these included: Per1, Per2, Arc, Homer2, Creb1, Grm3, Fosb, Gabrb3, Adra2a, Ntrk2, Cry1, Penk, Cartpt, Adcy1, Npy1r, Htr1a, Drd1a, Gria1, andPDYN。TopPluster分析发现，与尼古丁，氯胺酮和dronabinol的药物作用相关的基因，母体NAC表达谱均显着富集。途径分析表明，产后NAC富含RNA处理，CNS开发/分化和转录调控。加权基因共表达网络分析（WGCNA）确定了转录因子的可能网络，包括NR1D1，PER2，FOSB，EGR1和NR4A1。产后状态涉及增加精神疾病的风险，MSET分析表明，产后NAC富含与抑郁症，躁郁症（BPD）和精神分裂症。Mental health related genes included:FABP7, Grm3, Penk, and Nr1d1. We confirmed via quantitative PCR Nr1d1, Per2, Grm3, Penk, Drd1a, and Pdyn. This study indicates for the first time that postpartum NAC involves large scale gene expression alterations linked to addiction and reward. Because the postpartum state also involves decreased response to drugs, the findings could provide insights into how to mitigate addictions. |
| SCZ Keywords | 精神分裂症，精神分裂症 |
| 8 | Hum. Mol. Genet. 2014 Dec 23: 6495-511 |
| PMID | 25027319 |
| Title | 在精神分裂症和自闭症谱系障碍和小鼠行为研究中鉴定的Fabp3，5和7基因变体的功能表征。 |
| 抽象的 | 脂质代谢的障碍与精神病有关。我们先前报道了脂肪酸结合蛋白7的基因之间的关联（FABP7) and精神分裂症。Furthermore, we identified and reported several rare non-synonymous polymorphisms of the brain-expressed genes FABP3, FABP5 andFABP7从精神分裂症和自闭症谱系障碍（ASD），已知可以分散遗传结构的疾病。在这里，我们进行了进一步的研究，以更好地了解这些基因对精神分裂症and ASD. In postmortem brains, we detected altered mRNA expression levels of FABP5 in精神分裂症, and ofFABP7in ASD and altered FABP5 in peripheral lymphocytes. Using a patient cohort, comprehensive mutation screening identified six missense and two frameshift variants from the three FABP genes. The two frameshift proteins, FABP3 E132fs andFABP7N80F，形成的细胞聚集体，在培养细胞中表达时不稳定。具有预测可能破坏结果的四个错义突变体显示细胞内定位没有变化。检查配体结合特性，FABP7S86G andFABP7V126L lost their preference for docosahexaenoic acid to linoleic acid. Finally, mice deficient in Fabp3, Fabp5 andFABP7were evaluated in a systematic behavioral test battery. The Fabp3 knockout (KO) mice showed decreased social memory and novelty seeking, andFABP7KO小鼠表现出多动和焦虑相关的表型，而Fabp5 KO小鼠没有明显的表型。总之，脑表达的FABP的干扰可以代表一种基本的疾病机制精神分裂症and ASD sufferers. |
| SCZ Keywords | 精神分裂症，精神分裂症 |
| 9 | Front Behav Neurosci 2014 -1 8：110 |
| PMID | 24765068 |
| Title | 内侧前额叶皮层：与躁郁症和精神分裂症相关的基因已改变了高度社交母体表型的表达。 |
| 抽象的 | 向母性的过渡涉及CNS的变化，以改变社交状态和情感状态。但是，这些变化也使女性有产后抑郁症和精神病的风险，这会损害育儿能力，并对儿童产生不利影响。因此，基因核心子集的表达和相互作用的变化对于健康的母体表型的出现可能至关重要，但是同一基因的不适当变化可能会使女性处于产后疾病的风险。这项研究评估了内侧前额叶皮层（MPFC）的微阵列基因表达变化，该区域涉及孕产妇行为和精神疾病。将产后小鼠与雌性饲养并分离出相同持续时间分离的处女对照组进行了比较。使用模块化的单集富集测试（MSET），我们发现母体MPFC的遗传景观与与与之相关的基因数据库具有统计相似性精神分裂症（5组中的5个）和躁郁症（BPD，3组中的3组）。与先前对母体外侧隔膜（LS）和内侧前区域（MPOA）的研究相反，自闭症和抑郁症连接基因的富集并不显着（9组中的2个，4组中的0组）。在与多种疾病相关的基因中，有脂肪酸结合蛋白7（FABP7），谷氨酸代谢受体3（GRM3），血小板衍生的生长因子，β多肽（PDGFRB）和核受体亚家族1，D组，成员1（NR1D1）。RT-QPCR证实了这些基因的变化以及FMS样酪氨酸激酶1（FLT1）和Proenkephalin（PENK）。系统级别的方法揭示了发育基因网络在建立母体表型中的参与，并间接提出了许多microRNA和转录因子在中介表达变化中的作用。总之，这项研究表明，塑造健康孕产妇大脑的基因子集也可能在心理健康障碍中失调，并使女性处于产后精神病的风险，并具有各个方面精神分裂症and BPD. |
| SCZ Keywords | 精神分裂症，精神分裂症 |
| 10 | Neurosci. Res. 2016 Jan 102: 47-55 |
| PMID | 25205626 |
| Title | 脂肪酸结合蛋白和神经系统：它们对精神状况的影响。 |
| 抽象的 | The brain is rich in lipid and fatty molecules. In this review article, we focus on fatty acid binding proteins (Fabps) that bind to fatty acids such as arachidonic acid and docosahexianoic acid and transfer these lipid ligands within the cytoplasm. Among Fabp family molecules, Fabp3, Fabp5, andFABP7are specifically localized in neural stem/progenitor cells, neurons and glia in a cell-type specific manner. Quantitative trait locus analysis has revealed thatFABP7与用作精神疾病的内表型（例如精神分裂症。fabp5和FABP7play important roles on neurogenesis and differentially regulate acoustic startle response and PPI. However, other behavior performances including spatial memory, anxiety-like behavior, and diurnal changes in general activity were not different in mice deficient forFABP7或fabp5。考虑到脂肪酸在神经发生中的重要性，我们要强调，通过FABPS的脂质营养及其动态性在心理条件下起着重要作用。这可能提供一个很好的例子，说明营养环境如何影响分子水平的精神病。 |
| SCZ Keywords | 精神分裂症，精神分裂症 |
| 11 | 精神分裂。res。2016年3月171日：225-32 |
| PMID | 26792082 |
| Title | Fatty acid composition and fatty acid binding protein expression in the postmortem frontal cortex of patients with schizophrenia: A case-control study. |
| 抽象的 | N-3多不饱和脂肪酸（PUFAS）的水平异常，尤其是Docosahexaenoic酸（DHA），已在验尸后皮层，尤其是眶额皮质中，尤其是甲状腺皮质，尤其是甲状腺素酸（尤其是眶额皮质）患者。精神分裂症。Altered mRNA expression of fatty acid binding protein (FABP) 5 andFABP7has likewise been reported. 这项研究调查了额叶皮层[Brodmann区域（BA）8]和Fabp3、5和7的mRNA表达中的PUFA是否不同精神分裂症(n=95) and unaffected controls (n=93). In contrast to previous studies, no significant differences were found in DHA between the groups. Although arachidonic acid (AA) levels were significantly decreased in the精神分裂症group, no association was found between AA and精神分裂症关于逻辑回归分析。仅Fabp3表达在精神分裂症组比对照组。仅在两个饱和脂肪酸，贝尼酸和木质酸和FABP3表达之间观察到显着的逆关联。 We found no evidence that major PUFA levels in BA8 are involved in the etiology of精神分裂症。尽管FabP3表达与任何主要的PUFA都没有相关，但它可能在BA8病理中起新颖的作用精神分裂症。 |
| SCZ Keywords | 精神分裂症，精神分裂症 |
| 12 | Glia 2016 Jan 64: 48-62 |
| PMID | 26296243 |
| Title | 星形胶质细胞表达的FABP7调节皮质神经元的树突形态和兴奋性突触功能。 |
| 抽象的 | Fatty acid binding protein 7 (FABP7) expressed by astrocytes in developing and mature brains is involved in uptake and transportation of fatty acids, signal transduction, and gene transcription.FABP7knockout (FABP7KO) mice show behavioral phenotypes reminiscent of human neuropsychiatric disorders such as精神分裂症。但是，直接证据表明如何FABP7deficiency in astrocytes leads to altered brain function is lacking. Here, we examined neuronal dendritic morphology and synaptic plasticity in medial prefrontal cortex (mPFC) ofFABP7KO mice and in primary cortical neuronal cultures. Golgi staining of cortical pyramidal neurons inFABP7KO小鼠发现与野生型（WT）小鼠相比，树突状形态异常和脊柱密度降低。在与共同培养的原代皮质神经元中也观察到了异常的树突形态FABP7- 缺乏培养的星形胶质细胞和神经元FABP7KO星形胶质细胞调节培养基。MPFC的兴奋性突触数量减少FABP7KO mice and in neurons co-cultured withFABP7KO星形胶质细胞。因此，MPFC中的锥体细胞中的大脑切片中的全细胞电压钳记录都表明，动作势与潜在的微型兴奋性兴奋性突触后电流（MEPSC）均均减少FABP7KO mice. Moreover, transplantation of WT astrocytes into the mPFC ofFABP7KO mice partially attenuated behavioral impairments. Collectively, these results suggest that astrocyticFABP7is important for dendritic arbor growth, neuronal excitatory synapse formation, and synaptic transmission, and provide new insights linkingFABP7，脂质稳态和神经精神疾病，导致新的治疗干预措施。 |
| SCZ Keywords | 精神分裂症，精神分裂症 |